Further Ultrastructural Observations of Virus Morphogenesis and Myelin Pathology in JHM Virus Encephalomyelitis

Abstract

Groups of 3, 17, and 28-day-old Swiss mice were inoculated intracerebrally with JHM virus, the neurotropic strain of mouse hepatitis virus (MHV), and studied serially by virologic and morphologic techniques. Beginning 2--5 days post-inoculation, all groups of infected mice developed CNS lesions which were destructive in the 3-day-old group and demyelinative in the 17 and 28-day-old animals. Infectious virus could be isolated from the brain, spinal cord, and liver. Electron microscopy demonstrated the virus to be pantropic in the CNS with virions occurring within ependymal cells, astrocytes, neurons, oligodendrocytes, endothelial cells, and cell of haematogenous origin. Giant cell formation was a constant feature. In regions of demyelination, oligodendrocytes exhibited a propensity to proliferative aberrant membrane. Myelin degradation was accompanied by membrane vesiculation and by the stripping action of macrophages. The lesions were not due to CNS elements in the inoculum since in animals inoculated with normal CNS suspensions from appropriate age groups failed to show lesions. The morphogenesis of JHM virions was followed ultrastructurally as was the formation of syncytia in the different cell types. In addition to delineating virus morphogenesis and myelin pathology, the results underscore the pantropic nature of JHM virus in the CNS, the synstemic nature of the infection, and that oligodendrocytes were the principal targets.

The Pathogenesis of Murine Coronavirus Infection of the Central Nervous System

“…As with other demyelinating diseases118, 119, ultrastructural analysis of MHV induced demyelinating lesions reveal myelin laden macrophages stripping and engulfing myelin120 (Figure 1). During chronic infection, macrophages are spatially associated within demyelinating white matter lesions of the spinal cord and are critical to demyelination.…”

In vivo and in vitro Models of Demyelinating Diseases

“…the diameter of the helical nucleocapsid of the paramyxoviruses, measuring 15-19 nm [24,32,33], is about double the width of the coronavirus cores. According to another recent interpretation, the coronavirus nucleocapsid structure is described as a circular, dense, inner component, about 60 nm in diameter [7], Our new evidence, coupled with information ob tained on disrupted negatively stained 229E virions [29,31] and on another representative of the group [30], indicate that the architecture of the coronaviruses simulates that of the orthomyxo-and paramyxoviruses, although the coronaviruses, unlike the other two groups, possess a single-stranded RNA genome of the + sense. From this observation it may be con cluded that polarity of the RNA genome and helical conformation of the nucleoprotein are not necessarily interrelated.…”

The chemokine receptor CXCR2 and coronavirus-induced neurologic disease

“…As with other demyelinating diseases (Epstein et al, 1983; Field and Raine, 1966), ultrastructural analysis of MHV-induced demyelinating lesions reveal myelin laden macrophages stripping and engulfing myelin (Fleury et al, 1980). During chronic infection, macrophages are spatially associated within demyelinating white matter lesions of the spinal cord and are critical to demyelination.…”